First patient dosed in unique biomarker guided Ph III study of enzastaurin + R-CHOP in high-risk diffuse large B-cell lymphoma (DLBCL)

On 4/3/2018, Denovo Biopharma LLC, announced dosing of the first patient in its pivotal Phase 3 ENGINE trial.   The ENGINE trial is a global, randomized, double-blind, registrational study evaluating the efficacy of DB102 (enzastaurin) in combination with R-CHOP versus R-CHOP alone in DLBCL patients with or without the biomarker DGM1.   The study is to enroll 235 patients and the primary outcome measure is overall survival in patients with DGM1.

Enzastaurin has an interesting history. While it demonstrated considerable efficacy in animal models, it achieved minimal benefit in a number of Ph II and Ph III trials. However there were clusters of successes in several trials. In one Ph II trial in patients with relapsed diffuse B cell lymphoma and in patients with high grade recurrent gliomas 4 of 55 patients showing progress free survival for over 50 months. In another patients with relapsed and refractory mantle cell lymphoma, 2 patients of a total of 60 were able to achieve freedom from progression after enzastaurin administration for more than two years  .http://www.croh-online.com/article/S1040-8428(17)30053-7/fulltext

When Denovo acquired  worldwide rights to develop, produce, and market enzastaurin, along with the intellectual property rights and other data in 2014 it noted enzastaurin had failed to meet primary endpoints in a Ph III study. Denovo pointed out however, that a group of patients showed significantly improved progression-free survival. The company said it planned to run genetic analysis of the group using its biomarker discovery platform to determine biomarkers which could explain the patients’ responsiveness to the treatment. The ENGINE trial incorporates those efforts.

"The initiation of this innovative biomarker driven trial marks a significant milestone for Denovo Biopharma. Importantly, the addition of DB102 to R-CHOP may offer improved benefit over R-CHOP alone in patients with high-risk DLBCL identified by a biomarker," said  Ronald Shazer, M.D., Chief Medical Officer of Denovo Biopharma. "Although treatment with R-CHOP is curative in the majority of patients with low-risk DLBCL, the same cannot be said for high-risk DLBCL and alternative treatments are urgently needed for these patients."

R-CHOP – is an abbreviation for a chemotherapy combination that is used to treat non-Hodgkin lymphoma and mantle cell lymphoma and is being studied in the treatment of other types of cancer. It includes the drugs rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone.

The ENGINE trial will provide insight into how well Denovo's biomarker discovery platform performs in clinical trials.